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Biomedical subjects

C R Wilson

Publications and source records attributed to C R Wilson.

At least 37 records · Page 2Linked to original sources
PubMed1999

Elevated salivary cortisol in the evening in healthy elderly men and women: correlation with bone mineral density.

BACKGROUND: Aging is associated with a loss of bone mineral density (BMD) in men and women. Loss of BMD can also be caused by hypercortisolemia in men or women at any age. This study measured salivary cortisol at 2300 h and 0700 h as indices of cortisol secretory activity in 228 elderly, community-dwelling subjects. Salivary cortisol results were correlated with BMD. We hypothesized that salivary cortisol is elevated at 2300 h in elderly people, and that salivary cortisol will correlate negatively with BMD. METHODS: Saliva was sampled at 2300 h (nadir in circadian rhythm) and 0700 h (peak in circadian rhythm) in 130 men (70.7 +/- 0.4 years old) and 98 women (70.0 +/- 0.4 years old); approximately half of the women were receiving hormone replacement therapy (HRT). BMD was measured by dual energy x-ray absorptiometry. RESULTS: Salivary cortisol at 2300 h was significantly elevated in men (2.3 +/- 0.1 nmol/L) and women (2.1 +/- 0.1 nmol/L) as compared to 73 younger controls (1.2 +/- 0.1 nmol/L; 37 +/- 1 year old). Salivary cortisol at 0700 h was not different between older subjects and younger controls. There was a significant negative correlation of lumbar (L2-4) BMD and 2300 h salivary cortisol in older women (r = -0.20, p = .05; n = 98); this correlation was significant only in women not on HRT. There was a highly significant negative correlation of lumbar (L2-4) BMD and 0700 h salivary cortisol in older men (r = -0.31, p = .0003). CONCLUSIONS: Salivary cortisol is a simple, nonstressful method for assessing activity of the hypothalamic-pituitary-adrenal (HPA) axis in the elderly population. A major finding was an elevation in the late night nadir in cortisol secretion. We also suggest that elevated cortisol secretion in elderly people may contribute to the age-related loss in bone mineral density and that this effect is prevented by HRT.

Aged↗
PubMed1999

Plasma leptin and insulin levels in weight-reduced obese women with normal body mass index: relationships with body composition and insulin.

Obesity is a complex disease with multiple features that has confounded efforts to unravel its pathophysiology. As a means of distinguishing primary from secondary characteristics, we compared levels of fasting plasma leptin and insulin in a cohort of weight-reduced obese women who have attained and maintained a normal BMI for more than 1 year with the levels in cohorts of never-obese and currently obese women. Weight-reduced obese women showed decreased plasma concentrations of leptin and insulin compared with obese women, but these levels remained significantly higher than those of never-obese women. Plasma leptin levels were highly correlated with plasma insulin levels (r = 0.60, P < 0.001). To further explore relationships with body composition, total body fat was determined by dual-energy X-ray absorptiometry and body fat distribution by computed tomography in subsets of these groups. Weight-reduced obese women had a significantly greater percent body fat and subcutaneous abdominal fat mass than did the never-obese women, and these were highly correlated with plasma leptin (r = 0.90, P < 0.001, and r = 0.52, P < 0.001, respectively). In these weight-reduced obese women, visceral fat mass was similar to that of the never-obese. The insulin sensitivity index and first-phase insulin response were also comparable. These results demonstrate that higher leptin levels in weight-reduced obese women are related to the higher total fat and particularly the subcutaneous fat masses. Normalization of visceral fat mass in the weight-reduced obese was accompanied by normalization of insulin sensitivity index and first-phase insulin response. This study suggests that increases in plasma leptin and insulin in obesity are secondary features of the obese state.

Absorptiometry, Photon↗
PubMed1998

An induced blood pressure rise does not alter upper airway resistance in sleeping humans.

Sleep apnea is associated with episodic increases in systemic blood pressure. We investigated whether transient increases in arterial pressure altered upper airway resistance and/or breathing pattern in nine sleeping humans (snorers and nonsnorers). A pressure-tipped catheter was placed below the base of the tongue, and flow was measured from a nose or face mask. During non-rapid-eye-movement sleep, we injected 40- to 200-microgram i.v. boluses of phenylephrine. Parasympathetic blockade was used if bradycardia was excessive. Mean arterial pressure (MAP) rose by 20 +/- 5 (mean +/- SD) mmHg (range 12-37 mmHg) within 12 s and remained elevated for 105 s. There were no significant changes in inspiratory or expiratory pharyngeal resistance (measured at peak flow, peak pressure, 0.2 l/s or by evaluating the dynamic pressure-flow relationship). At peak MAP, end-tidal CO2 pressure fell by 1.5 Torr and remained low for 20-25 s. At 26 s after peak MAP, tidal volume fell by 19%, consistent with hypocapnic ventilatory inhibition. We conclude that transient increases in MAP of a magnitude commonly observed during non-rapid-eye-movement sleep-disordered breathing do not increase upper airway resistance and, therefore, will not perpetuate subsequent obstructive events.

Adrenergic alpha-Agonists↗
PubMed1998

Assessment of inspiratory flow limitation invasively and noninvasively during sleep.

To define the standard of airway flow limitation, pharyngeal pressure and flow rate were measured during wakefulness and sleep in seven habitual snorers with widely varying degrees of sleep-induced increases in upper airway resistance. Inspiratory pressure:flow relationships were used to group breaths into four categories of flow limitation, including linear (Level 1), mildly alinear (Level 2), constant flow rate with no pressure dependence (Level 3), and decreasing flow rate throughout significant portions of inspiration, i.e., negative pressure dependence (Level 4). These pressure:flow rate gold standards of flow limitation were used to evaluate a flow limitation index derived from the time profile (or "shape") of three noninvasive estimates of flow rate: (1) pneumotach flow rate, (2) differentiated sum respiratory inductance plethysmography (RIP), and (3) nasal pressure. A nonflow limited template for each of these noninvasive measurements was taken from awake breaths and the difference in area determined between the template breath and each of the noninvasive signals measured during nonrapid eye movement (NREM) sleep. The noninvasive flow limitation indices were found to be effective in differentiating severe types of inspiratory flow limitation, i.e., Level 1 versus Level 3 or Level 4 (sensitivity/specificity > 80%). On the other hand, these indirect indices were not able to consistently detect mild levels of flow limitation (Level 1 versus Level 2; sensitivity/specificity = 62 to 72%); nor were these noninvasive estimates of flow rate "shape" sensitive to breaths with a high but fixed resistance throughout inspiration. The area index derived from measurements of pressure at the nares (Pn) was the most sensitive, nonperturbing, noninvasive measure of flow rate and flow limitation, and we recommend its use for recognizing most of the common types of moderate to severe levels of airway flow limitation in sleeping subjects.

Adult↗
PubMed1996

Biomechanical analysis of thoracolumbar interbody constructs. How important is the endplate?

STUDY DESIGN: A biomechanical study of human cadaveric thoracic vertebral bodies was conducted using several anterior fusion options subjected to axial loads. This study emphasized the contribution of the endplate to resistance of graft subsidence. OBJECTIVES: To determine the importance of the vertebral endplate in resisting subsidence of various constructs into the vertebral body; the relative efficacy of potential alternative graft constructs such as iliac crest, ribs, humerus, and titanium mesh cage; and the importance of bone mineral content, vertebral level, and cross-sectional graft area on construct subsidence. SUMMARY OF BACKGROUND DATA: As the fixation length of anterior and posterior spinal constructs is reduced, load sharing of the anterior column has become more important to reduce failure of the shorter devices. Several alternative graft constructs and surgical techniques have been used for reconstruction of the anterior column. There exist little comparative data as to whether any of these constructs are superior and whether the vertebral endplate contributes significantly to the integrity of the construct. METHODS: Sixty-three isolated human cadaveric vertebral bodies from T3 to T12 were used to test seven different constructs in direct axial load onto prepared endplates with an electrohydraulic testing device. These constructs were: 1) titanium mesh cage (17 x 22 mm) on intact endplate, 2) C-shaped humerus on intact endplate, 3) tricorticated iliac graft in "tee configuration" on intact endplate, 4) tricorticated iliac graft in cancellous trough, 5) triple rib strut graft, 6) single rib on endplate, and 7) single rib on cancellous body. Dual X-ray absorptiometry assessment of bone mineral content was performed. A uniaxial load was applied with force and displacement data collected to determine maximal load to "failure" of the vertebral body. RESULTS: Preservation of vertebral endplate did not significantly increase the resistance to graft subsidence. The titanium cage construct provided the greatest resistance to axial load. CONCLUSIONS: Preservation of the vertebral endplate may not offer a significant biomechanical advantage in reconstructing the anterior column. Several alternative constructs are mechanically equivalent.

Adult↗
PubMed1996

Unusual ligand binding at the active site domain of an engineered mutant of subtilisin BL.

As an attempt to recruit the third calcium binding site of thermitase into subtilisin BL, a Bacillus lentus alkaline protease (BLAP), the amino acid sequence from position 50 to 60 and position 92 was modified to the equivalent amino acids in thermitase. The resulting protein, designated BLAPm109, exhibited unusual biochemical features. Peptide mapping and gel electrophoresis revealed that two protein species co-purify in a ratio of about 1:1. Form 1 consisted of a single polypeptide of 269 amino acid residues. Form 2 was the same protein but with an internal peptide bond cleavage at the C-terminus of position 54. On electropherograms a dimer of Form 1 and Form 2 was also detectable. A zymogram showed that all three molecular species were catalytically active. From this protein mixture, crystals suitable for X-ray analysis were nevertheless obtained. SDS-PAGE of protein recovered from a crystal revealed that only Form 2 appears. in the crystal. The space group for this crystal was P21 with unit cell dimensions of a=42 angstroms, b=58 angstroms, c=47 angstroms and beta = 106.3 degrees. Examination of the preliminary electron density map revealed that the "thermitase loop" from 50 to 60 departs from the surface of the protein and winds through the active site of a symmetry-related copy of the asymmetric unit.

Amino Acid Sequence↗
PubMed1996

Frequency and volume thresholds for inhibition of inspiratory motor output during mechanical ventilation.

We quantified volume and frequency thresholds necessary for the inhibition of respiratory motor output during prolonged normocapnic mechanical ventilation in healthy subjects during wakefulness (n = 7) and NREM sleep (n = 5). Subjects were ventilated at eupneic frequency (fR) with 3 min step-wise increases in tidal volume (VT), or at eupneic VT with step-wise increases in fR, or by combinations of these two parameters. Inhibition of respiratory motor output was determined using mask pressure and, when available, esophageal pressure and diaphragmatic EMG. During wakefulness, the volume threshold (at eupneic fR) averaged 969 +/- 94 ml or 1.3-1.4 times the average eupneic tidal volume; the frequency threshold (at eupneic VT was 14.1 +/- 0.7 min-1 or 1.2 times the average eupneic frequency. The volume threshold was reduced when MV was provided at an fR above the eupneic value, and the frequency threshold was decreased when MV was provided at a VT above the eupneic level. During NREM sleep (n = 5) the volume threshold for inhibition was 835 +/- 108 ml or 1.4-1.5 times eupneic VT. The inhibitory thresholds for VT and fR were reproducible upon repeat trials within subjects. We conclude that inhibition of respiratory motor output during prolonged normocapnic mechanical ventilation in wakefulness or NREM sleep is highly sensitive to changes in ventilator VT, fR and their combination.

Adult↗
PubMed1996

Apnea prolongation via short-term inhibition.

Central apneas during sleep are frequently of longer duration than predicted and persist despite high levels of chemical stimuli. We provide evidence that suggests that this apnea prolongation represents a central inertia in the control system mediated by reciprocal inhibition of inspiration.

Animals↗
PubMed1995

Prediction of fatigue screw loosening in anterior spinal fixation using dual energy x-ray absorptiometry.

STUDY DESIGN: A biomechanical study was performed to investigate a relation between the bone mineral density of the vertebral body and the number of loading cycles to induce fatigue loosening of an anterior vertebral screw. OBJECTIVES: The objective of this study was to investigate the potential usefulness of dual energy x-ray absorptiometry of measuring bone mineral density of the vertebral body in predicting the fatigue loosening of th anterior vertebral screw. SUMMARY OF BACKGROUND DATA: Loosening of the vertebral body screw is a well know failure in spinal instrumentation, and more commonly observed than pullout failure. The relation between bone mineral density and pullout strength of the screw has been investigated previously, but no studies are available on the fatigue loosening in anterior spinal fixation. METHODS: Bone mineral density was measured using dual energy x-ray absorptiometry and the screw loosening was produce by a cyclic loading in the cephalad-caudal direction. Screw loosening was defined as 1 mm displacement of the screw relative to bone, and the number of loading cycles to induce the screw loosening was obtained and statistically correlated with bone mineral density. RESULTS: There was a positive correlation between the number of loading cycles to induce screw loosening and bone mineral density (R = 0.8, P < 0.01). The average number of loading cycles to induce screw loosening was significantly less for specimens with bone mineral density < 0.45 g/cm2 compared to those with bone mineral density > or = g/cm2. CONCLUSIONS: These findings suggest that bone mineral density may be a good predictor of anterior vertebral screw loosening. Bone mineral density < 0.45 g/cm2 may be critical value of loosening of the anterior vertebral body screw. However, further biomechanical and clinical studies are required before using threshold value clinically.

Absorptiometry, Photon↗
PubMed1995

Observations on nursing home residents with a history of hip fracture.

The authors evaluated nursing home residents with a prior history of hip fracture for osteopenia and its risk factors, and attempted to learn to what extent the residents' bone status had been considered by their primary care physicians. Thirty-one hip fracture residents in the Milwaukee VA nursing home were studied to determine their status with regard to bone mineral density of the proximal femur, and the following risk factors or predictors of osteopenia: history of smoking; history of fractures; calcium and vitamin D intake; underweight; immobility; hypogonadism; and administration of drugs that may accelerate bone demineralization. Data were also collected on the evaluation and management of the post hip fracture residents in three other nursing homes. In the Milwaukee nursing home, out of 31 hip fracture survivors, 74% had sustained a hip fracture before admission to the nursing home; 29% had a history of second fracture. In 84% of patients, there was no mention of osteopenia in the active medical problem list and, therefore, there was no intervention plan in place to improve or prevent further bone loss. Thirty-two percent were underweight, 36% were currently smoking, 55% were immobile, 64% were consuming at least one medication that might increase bone loss, calcium intake was less than 1,000 mg daily in 52%, and 66% were hypogonadal (serum testosterone level less than 300 ng/dL). Chart reviews of the hip fracture survivors at three other nursing homes revealed similar findings. Approximately 5-15% of nursing home residents are hip fracture survivors. They usually have severe osteopenia and multiple risk factors for further bone loss and future fractures.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Strength of anterior vertebral screw fixation in relationship to bone mineral density.

A biomechanical study was performed to investigate the relationship among the pullout strength of anterior vertebral screw fixation, bone mineral density (BMD) of the vertebral body, screw insertion torque, and width of the vertebral body. BMD was measured using a dual energy x-ray absorptiometry unit. Screw insertion torque and width of the lumbar vertebrae were also measured before the pullout test. Pullout strength was significantly correlated with BMD (r = 0.85) and screw insertion torque (r = 0.47), but not with width of the vertebral body. Multiple regression analyses demonstrated better correlation between pullout strength and the other parameters (r = 0.886). A stepwise regression analysis showed that BMD is the most significant predictor of the pullout strength followed by width of the vertebral body, whereas screw insertion torque is not a significant predictor. Furthermore, the mean pullout strength of the grade I osteoporosis group was significantly greater than that of grade II or III osteoporosis group.

Absorptiometry, Photon↗
PubMed1994

Comparison of nuclear magnetic resonance spectroscopy with dual-photon absorptiometry and dual-energy X-ray absorptiometry in the measurement of thoracic vertebral bone mineral density: compressive force versus bone mineral.

31P nuclear magnetic resonance spectroscopy (NMRS) measurements were made on human T2 and T3 vertebral bodies. The bone mineral content (BMC) of isolated vertebral bodies minus the posterior elements and disks was measured using (1) NMRS on a 3.5 T, 85 mm bore GE Medical Systems NT-150 superconducting spectrometer, (2) a Lunar Corporation DPX-L dual-energy X-ray absorptiometry (DXA) scanner in an anterior-posterior (AP) orientation, (3) a Norland Corporation XR26 DXA scanner, also in an AP direction, and (4) a Norland Corporation model 2600 dual-photon absorptiometry (DPA) densitometer in both the AP and superior-inferior (SI) directions. Vertebral body volumes were measured using a water displacement technique to determine volume bone mineral densities (VBMD). They were then compressed to failure using an electrohydraulic testing device, followed by ashing in a muffle furnace at 700 degrees C for 18 h. Correlations of BMC between NMRS and DPA, DXA and ashing were excellent (0.96 < or = r < or = 0.99); in a one-way analysis of variance (ANOVA) test, means were not statistically different at a p level of 0.757. The correlations of VBMD between NMRS and the other methods were not as good (0.83 < or = r < or = 0.95); in a one-way ANOVA test, means were not statistically different at a p level of 0.089. BMC was a better predictor of ultimate compressive failure than VBMD for all six methods. For NMRS, the regression coefficient for BMC was r2 = 0.806, compared with r2 = 0.505 for VBMD. NMRS may prove an alternative to present methods of determining bone mineral.

Absorptiometry, Photon↗
PubMed1994

Phrenic afferent stimulation by bradykinin and the distribution of the inspiratory motor drive.

Activation of thin-fiber (groups III and IV) afferents from the diaphragm using capsaicin or ischemia increases the respiratory muscle activity. To assess whether bradykinin causes similar effects, we injected boluses of bradykinin into the phrenic artery of in situ, isolated and innervated left hemi-diaphragm preparations in 8 alpha-chloralose anesthetized, vagotomized, mechanically ventilated dogs. Inspiratory motor drive during spontaneous breathing attempts was assessed from the integrated EMG activity of several inspiratory muscles. Fifty micrograms of bradykinin increased peak integrated EMG activities of alae nasi to 110%, genioglossus to 189%, left diaphragm to 115% (P < 0.05) and parasternal to 109% (P < 0.01) of baseline activity 60 sec after the injection. Inspiratory time decreased by 10% (P < 0.01). The mean arterial blood pressure increased by about 10 mmHg. Responses were similar with 10, 25 and 100 micrograms of bradykinin. After left phrenicotomy, bradykinin did not affect inspiratory muscle EMG or respiratory timing. In conclusion, thin-fiber phrenic afferent activation by bradykinin exerts an excitatory but disproportionate influence on the inspiratory motor drive.

Animals↗
PubMed1994

Relations of endogenous anabolic hormones and physical activity to bone mineral density and lean body mass in elderly men.

OBJECTIVE: It has been proposed that declining activities of the somatotrophic or gonadotrophic axes, or sedentary life style, are partial causes for geriatric losses of bone mineral density (BMD) and of lean body mass (LBM). The present study tested these hypotheses by determining, in both free-living and institutionalized elderly men, the correlations of bone mineral density (BMD), total body bone mineral content (TBBMC) and lean body mass (LBM) with the following predictor variables: age, body mass index, body weight, serum insulin-like growth factor I (IGF-I), serum testosterone, habitual physical activity and mobility. SUBJECTS: Forty-nine independent, community-dwelling older men, and 49 men of similar age residing in two Veterans Administration extended care facilities. The age range was 58-95 years. MEASUREMENTS: Serum IGF-I and testosterone were measured by radioimmunoassay. Habitual physical activity in the independent men and mobility in the institutionalized men were estimated by standard instruments. LBM and bone status at nine skeletal sites were determined by dual X-ray absorptiometry. RESULTS: The BMD and TBBMC values of the free living men were 4-20% higher than those of the institutionalized men. In the independent old men, serum testosterone was the strongest predictor of BMD and TBBMC, while age was the only predictor of LBM. In the chronically institutionalized men, age, body weight and immobility were the strongest predictors of body composition, and testosterone was correlated only with femoral neck BMD. CONCLUSIONS: In aging independent men, low levels of testosterone are associated with demineralization of the skeleton. Immobility and under-weight are associated with the osteopenia of old men residing in nursing homes. In this cross-sectional study of elderly men, there was no evidence of a relation of the somatotrophic axis to bone status or LBM, or of the gonadotrophic axis to LBM.

Activities of Daily Living↗
PubMed1993

Strategy and implementation of a system for protein engineering.

This paper describes an overall view of an industrial protein engineering project from conception to successful completion. The choice of rational design was determined by the availability of an excellent three-dimensional crystal structure and the availability of information in the literature to define a strategy. The design strategy was refined extensively during the course of the project. The development of methods for mutagenesis, expression, verification, purification, and characterization of mutant enzymes is dictated in part by the enzyme property one chooses to modify and must be rapid yet accurate. Such an approach would be applicable to improve the stability of any other protein or enzyme. Using this approach, we successfully increased the stability of subtilisin BL over 10-fold at 50 degrees C with an overall success rate greater than 60%.

Bacillus↗